{"orpha":2609,"name":"Isolated complex I deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Isolated NADH-CoQ reductase deficiency","Isolated NADH-coenzyme Q reductase deficiency","Isolated NADH-ubiquinone reductase deficiency","Isolated mitochondrial respiratory chain complex I deficiency"],"definition":"Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2609/","orphanet_url":"https://www.orpha.net/en/disease/detail/2609","names":{"fr":{"name":"Déficit isolé en complexe I","synonyms":["Déficit isolé en NADH-CoQ réductase","Déficit isolé en NADH-coenzyme Q réductase","Déficit isolé en NADH-ubiquinone réductase","Déficit isolé en complexe I de la chaîne respiratoire mitochondriale"],"definition":"Une erreur rare héréditaire du métabolisme, causée par des mutations au niveau des gènes nucléaires et mitochondriaux codant pour les sous-unités ou les facteurs d'assemblage du complexe mitochondrial humain I (NADH : ubiquinone oxydo-réductase). Elle se caractérise par un large spectre de signes incluant une acidose lactique prononcée, souvent fatale, une cardiomyopathie, une leukoencéphalopathie, une myopathie pure et une hépatopathie avev tubulopathie. Le syndrome de Leigh, la neuropathie optique héréditaire de Leber et le syndrome MELAS font partie des nombreux phénotypes cliniques observés."},"de":{"name":"Isolierter Atmungskettendefekt im Komplex I","synonyms":["NADH-CoQ-Reduktase Mangel, isolierter","NADH-Coenzym-Q-Reduktase-Mangel, isolierter","NADH-Ubiquinon-Reduktase-Mangel, isolierter"],"definition":"Der isolierte Komplex I-Mangel ist ein seltener angeborener Stoffwechseldefekt, hervorgerufen durch Mutationen in nukleären oder mitochondrialen Genen, die für Untereinheiten oder Kofaktoren des menschlichen Mitochondrienkomplexes I kodieren (NADH: Ubiqinon-Oxidoreduktase). Charakteristisch ist ein weites Symptomspektrum, das ausgeprägte und häufig tödlich verlaufende Laktatazidosen, Kardiomyopathie, Leukoenzephalopathie, reine Myopathie und Hepatopathie mit Tubulopathie umfasst. Auch das Leigh-Syndrom, die Leber'sche hereditäre Optikusneuropathie und das MELAS-Syndrom wurden beobachtet (s.dort)."},"es":{"name":"Deficiencia aislada del complejo I","synonyms":["Deficiencia aislada de NADH-CoQ reductasa","Deficiencia aislada de NADH-coenzima Q reductasa","Deficiencia aislada de NADH-ubiquinona reductasa","Deficiencia aislada del complejo I de la cadena respiratoria mitocondrial"],"definition":"Es un error congénito del metabolismo poco frecuente debido a mutaciones en genes nucleares o mitocondriales que codifican subunidades o factores de ensamblaje del complejo I mitocondrial en humanos (NADH: ubiquinona oxidorreductasa). Está caracterizada por un amplio rango de síntomas que incluye una marcada acidosis láctica que a menudo resulta letal, miocardiopatía, leucoenfalopatía, miopatía pura y hepatopatía con tubulopatía. Entre los numerosos fenotipos clínicos observados se encuentran el síndrome de Leigh, la neuropatía óptica hereditaria de Leber y el síndrome de MELAS."},"it":{"name":"Deficit isolato del complesso I","synonyms":["Deficit isolato del complesso I della catena respiratoria mitocondriale","Deficit isolato di NADH-CoQ reduttasi","Deficit isolato di NADH-Coenzima Q reduttasi","Deficit isolato di NADH-ubichinone reduttasi"],"definition":"Il deficit isolato del complesso I (CI) è un difetto raro congenito del metabolismo, causato dalle mutazioni nei geni nucleari o mitocondriali che codificano le subunità o i fattori di assemblaggio del complesso I mitocondriale umano (NADH: ubichinone ossidoreduttasi). E' caratterizzato da diversi segni clinici, compresa una marcata acidosi lattica, spesso letale, una cardiomiopatia, una leucoencefalopatia, la miopatia pura e l'epatopatia con tubulopatia. I quadri clinici osservati sono la sindrome di Leigh, la neuropatia ottica ereditaria di Leber, la sindrome MELAS (si vedano questi termini)."},"nl":{"name":"Geïsoleerde complex I-deficiëntie","synonyms":["Geïsoleerde NADH-CoQ-reductasedeficiëntie","Geïsoleerde NADH-co-enzym Q-reductasedeficiëntie","Geïsoleerde NADH-ubiquinonreductasedeficiëntie","Geïsoleerde mitochondriale ademhalingsketencomplex I-deficiëntie"],"definition":"Geïsoleerde complex I (CI)-deficiëntie is een zeldzame aangeboren fout in het metabolisme als gevolg van mutaties in nucleaire of mitochondriale genen die coderen voor subeenheden of assemblagefactoren van het humane mitochondriale complex I (NADH:ubiquinone oxidoreductase) en wordt gekarakteriseerd door een breed gamma aan manifestaties waaronder uitgesproken en vaak fatale lactaatacidose, cardiomyopathie, leuko-encefalopathie, zuivere myopathie en hepatopathie met tubulopathie. Enkele van de vele klinische fenotypes die worden geobserveerd, zijn syndroom van Leigh, erfelijke opticusneuropathie van Leber en MELAS-syndroom (zie deze termen)."},"pt":{"name":"Deficiência de complexo I isolada","synonyms":["Deficiência de NADH-CoQ redutase","Deficiência de complexo 1 da cadeia respiratória mitocondrial"]},"pl":{"name":"Izolowany Niedobór reduktazy NADH-CoQ","synonyms":["Izolowany Niedobór kompleksu I mitochondrialnego łańcucha oddechowego","Izolowany Niedobór reduktazy NADH-koenzym Q","Izolowany Niedobór reduktazy NADH-ubikwinon"]},"cs":{"name":"Izolovaný deficit komplexu I","synonyms":["Izolovaný deficit NADH-CoQ reduktázy","Izolovaný deficit NADH-koenzym Q reduktázy","Izolovaný deficit NADH-ubichinon reduktázy","Izolovaný deficit mitochondriálního respiračního řetězce komplexu I"]},"uk":{"name":"Ізольований дефіцит комплексу I","synonyms":["Ізольований дефіцит комплексу I мітохондріального дихального ланцюга","Ізольований дефіцит NADH-коензиму Q-редуктази","Ізольований дефіцит NADH-CoQ-редуктази","Ізольований дефіцит НАДН-убіхінон-редуктази"],"definition":"Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome (see these terms)."},"zh":{"name":"孤立型复合物I缺乏","synonyms":["孤立型线粒体呼吸链复合物I缺乏症"]},"tr":{"name":"İzole kompleks I eksikliği","synonyms":["İzole NADH-CoQ redüktaz eksikliği","İzole NADH-koenzim Q redüktaz eksikliği","İzole NADH-ubikinon redüktaz eksikliği","İzole mitokondriyal solunum zinciri kompleksi I eksikliği"]}},"xrefs":[{"source":"OMIM","code":"252010","qualifier":"E","icd_relation":null,"validated":true},{"source":"OMIM","code":"301020","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"301021","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618222","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618224","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618225","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618226","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618228","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618229","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618230","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618232","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618233","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618234","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618236","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618237","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618238","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618240","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618241","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618242","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618244","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618245","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618246","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618247","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618250","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618251","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618253","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618776","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619003","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619170","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"619272","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620135","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.2Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"67580224"},{"source":"MONDO","code":"0100133","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537475","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1838979","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3908","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":936,"name":"Succinic acidemia","status":"inactive"},{"type":"Referred to","orpha":289527,"name":"OBSOLETE: Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency","status":"inactive"}],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":254846,"name":"Isolated oxidative phosphorylation complex disorder","classifications":[150,156]},{"orpha":225700,"name":"Mitochondrial disease with epilepsy","classifications":[156,181]},{"orpha":206966,"name":"Mitochondrial myopathy","classifications":[156,181]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"NDUFB11","name":"NADH:ubiquinone oxidoreductase subunit B11","gene_type":"gene with protein product","association":"Candidate gene tested in","status":"Not yet assessed","source":"26741492[PMID]","hgnc":"20372","ensembl":"ENSG00000147123","omim":"300403","loci":["Xp11.3"]},{"symbol":"TIMMDC1","name":"translocase of inner mitochondrial membrane domain containing 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28604674[PMID]","hgnc":"1321","ensembl":"ENSG00000113845","omim":"615534","loci":["3q13.33"]},{"symbol":"TMEM126B","name":"transmembrane protein 126B","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"27374773[PMID]_27374774[PMID]","hgnc":"30883","ensembl":"ENSG00000171204","omim":"615533","loci":["11q14.1"]},{"symbol":"FOXRED1","name":"FAD dependent oxidoreductase domain containing 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20858599[PMID]","hgnc":"26927","ensembl":"ENSG00000110074","omim":"613622","loci":["11q24.2"]},{"symbol":"MT-ND1","name":"mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"10775530[PMID]_16492986[PMID]","hgnc":"7455","ensembl":"ENSG00000198888","omim":"516000","loci":["mitochondria"]},{"symbol":"MT-ND2","name":"mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"12192017[PMID]_15781840[PMID]","hgnc":"7456","ensembl":"ENSG00000198763","omim":"516001","loci":["mitochondria"]},{"symbol":"MT-ND3","name":"mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"14705112[PMID]","hgnc":"7458","ensembl":"ENSG00000198840","omim":"516002","loci":["mitochondria"]},{"symbol":"NDUFA1","name":"NADH:ubiquinone oxidoreductase subunit A1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"17262856[PMID]_19185523[PMID]_21596602[PMID]_22644603[PMID]","hgnc":"7683","ensembl":"ENSG00000125356","omim":"300078","loci":["Xq24"]},{"symbol":"NDUFA11","name":"NADH:ubiquinone oxidoreductase subunit A11","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18306244[PMID]_22644603[PMID]","hgnc":"20371","ensembl":"ENSG00000174886","omim":"612638","loci":["19p13.3"]},{"symbol":"NDUFA6","name":"NADH:ubiquinone oxidoreductase subunit A6","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"30245030[PMID]","hgnc":"7690","ensembl":"ENSG00000184983","omim":"602138","loci":["22q13.2"]},{"symbol":"NDUFA9","name":"NADH:ubiquinone oxidoreductase subunit A9","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"41069424[PMID]","hgnc":"7693","ensembl":null,"omim":null,"loci":["1p36.13"]},{"symbol":"NDUFAF1","name":"NADH:ubiquinone oxidoreductase complex assembly factor 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"17557076[PMID]","hgnc":"18828","ensembl":"ENSG00000137806","omim":"606934","loci":["15q15.1"]},{"symbol":"NDUFAF2","name":"NADH:ubiquinone oxidoreductase complex assembly factor 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16200211[PMID]","hgnc":"28086","ensembl":"ENSG00000164182","omim":"609653","loci":["5q12.1"]},{"symbol":"NDUFAF3","name":"NADH:ubiquinone oxidoreductase complex assembly factor 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19463981[PMID]_22644603[PMID]","hgnc":"29918","ensembl":"ENSG00000178057","omim":"612911","loci":["3p21.31"]},{"symbol":"NDUFAF4","name":"NADH:ubiquinone oxidoreductase complex assembly factor 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18179882[PMID]_22644603[PMID]","hgnc":"21034","ensembl":"ENSG00000123545","omim":"611776","loci":["6q16.1"]},{"symbol":"NDUFAF5","name":"NADH:ubiquinone oxidoreductase complex assembly factor 5","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18940309[PMID]_22644603[PMID]","hgnc":"15899","ensembl":"ENSG00000101247","omim":"612360","loci":["20p12.1"]},{"symbol":"NDUFAF8","name":"NADH:ubiquinone oxidoreductase complex assembly factor 8","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"31866046[PMID]","hgnc":"33551","ensembl":"ENSG00000224877","omim":"618461","loci":["17q25.3"]},{"symbol":"NDUFB10","name":"NADH:ubiquinone oxidoreductase subunit B10","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28040730[PMID]","hgnc":"7696","ensembl":"ENSG00000140990","omim":"603843","loci":["16p13.3"]},{"symbol":"NDUFB3","name":"NADH:ubiquinone oxidoreductase subunit B3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22277967[PMID]_22499348[PMID]","hgnc":"7698","ensembl":"ENSG00000119013","omim":"603839","loci":["2q33.1"]},{"symbol":"NDUFB9","name":"NADH:ubiquinone oxidoreductase subunit B9","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22200994[PMID]","hgnc":"7704","ensembl":"ENSG00000147684","omim":"601445","loci":["8q24.13"]},{"symbol":"NDUFS1","name":"NADH:ubiquinone oxidoreductase core subunit S1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20382551[PMID]_22644603[PMID]","hgnc":"7707","ensembl":"ENSG00000023228","omim":"157655","loci":["2q33.3"]},{"symbol":"NDUFS2","name":"NADH:ubiquinone oxidoreductase core subunit S2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"15576045[PMID]_22644603[PMID]","hgnc":"7708","ensembl":"ENSG00000158864","omim":"602985","loci":["1q23.3"]},{"symbol":"NDUFS3","name":"NADH:ubiquinone oxidoreductase core subunit S3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22499348[PMID]","hgnc":"7710","ensembl":"ENSG00000213619","omim":"603846","loci":["11p11.2"]},{"symbol":"NDUFS4","name":"NADH:ubiquinone oxidoreductase subunit S4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"9463323[PMID]_22644603[PMID]","hgnc":"7711","ensembl":"ENSG00000164258","omim":"602694","loci":["5q11.2"]},{"symbol":"NDUFS6","name":"NADH:ubiquinone oxidoreductase subunit S6","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"15372108[PMID]_19259137[PMID]_22644603[PMID]","hgnc":"7713","ensembl":"ENSG00000145494","omim":"603848","loci":["5p15.33"]},{"symbol":"NDUFS7","name":"NADH:ubiquinone oxidoreductase core subunit S7","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22644603[PMID]","hgnc":"7714","ensembl":"ENSG00000115286","omim":"601825","loci":["19p13.3"]},{"symbol":"NDUFS8","name":"NADH:ubiquinone oxidoreductase core subunit S8","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22499348[PMID]_22644603[PMID]","hgnc":"7715","ensembl":"ENSG00000110717","omim":"602141","loci":["11q13.2"]},{"symbol":"NDUFV1","name":"NADH:ubiquinone oxidoreductase core subunit V1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22644603[PMID]","hgnc":"7716","ensembl":"ENSG00000167792","omim":"161015","loci":["11q13.2"]},{"symbol":"NDUFV2","name":"NADH:ubiquinone oxidoreductase core subunit V2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"12754703[PMID]_22644603[PMID]_26008862[PMID]","hgnc":"7717","ensembl":"ENSG00000178127","omim":"600532","loci":["18p11.22"]},{"symbol":"NUBPL","name":"NUBP iron-sulfur cluster assembly factor, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20818383[PMID]_22644603[PMID]_23553477[PMID]","hgnc":"20278","ensembl":"ENSG00000151413","omim":"613621","loci":["14q12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive","Mitochondrial inheritance","X-linked dominant"],"onset":["All ages"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_15190193[PMID]_20818732[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2017-07-01","source":"30095618[PMID]_9463323[PMID]","terms":[{"hpo":"HP:0011923","label":"Decreased activity of mitochondrial complex I","frequency":"Obligate (100%)","criteria":null},{"hpo":"HP:0008316","label":"Abnormal mitochondria in muscle tissue","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001298","label":"Encephalopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012748","label":"Focal T2 hyperintense brainstem lesion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001943","label":"Hypoglycemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003542","label":"Increased circulating pyruvate concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002352","label":"Leukoencephalopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003737","label":"Mitochondrial myopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000543","label":"Optic disc pallor","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001138","label":"Optic neuropathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007704","label":"Paroxysmal involuntary eye movements","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000114","label":"Proximal tubulopathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000817","label":"Reduced eye contact","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000618","label":"Blindness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000819","label":"Diabetes mellitus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025116","label":"Fetal distress","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null}]}}